脑梗死患者MTHFR基因C677T多态性与同型半胱氨酸水平的相关性

Correlationship between homocysteine level and MTHFR gene C677T polymorphism in patients with cerebral infarction

目的探讨糖尿病性脑梗死患者和非糖尿病性脑梗死患者亚甲基四氢叶酸还原酶(MTH-FR)基因C677T多态性特点及其与血浆同型半胱氨酸(Hcy)水平的相关性。方法收集2016年6月至2018年5月于佛山市第一人民医院神经内科及康复医学病区的脑梗死住院患者256例(病例组)及体检中心健康对照者208例(对照组),应用PCR-RFLP方法检测MTHFR基因C677T多态性,同时采用循环酶法检测血浆Hcy水平,对不同组别MTHFR基因型分布进行分析比较,并比较不同组别及不同基因型人群之间血浆Hcy水平的差异。结果 256例脑梗死患者中,CC型136例(53.1%),CT型89例(34.8%),TT型31例(12.1%),与对照组的分布差异具有统计学意义(χ~2=12.821,P <0.001),病例组T等位基因频率显著高于对照组(29.5%vs. 19.2%,χ~2=12.927,P <0.001)。糖尿病脑梗死患者与非糖尿病脑梗死患者MTHFR基因型分布差异具有统计学意义(χ~2=16.667,P <0.001),糖尿病组T等位基因显著高于非糖尿病组(43.4%vs.24.5%,χ~2=17.183,P <0.001)。病例组脑梗死患者总体血浆Hcy水平以及各基因型患者的血浆Hcy水平均显著高于对照组(P <0.05),其中病例组TT型患者的Hcy水平显著高于CC型及CT型(F=26.291,P <0.001)。糖尿病脑梗死患者血浆Hcy平均水平低于非糖尿病脑梗死患者,但差异无统计学意义(t=1.578,P=0.116),其中糖尿病组TT型患者血浆Hcy水平显著低于非糖尿病组(t=2.929,P=0.007)。结论MTHFR基因TT型与血浆Hcy升高相关,可能是脑梗死发生的危险因素,其中TT型糖尿病患者在血浆Hcy水平较低的情况下即可能发生脑梗死,应引起临床重视。

Objective To investigate the correlationship between plasma homocysteine(Hey) level and C677 T gene polymorphism of methylene tetrahydrofolate reductase(MTHFR) in cerebral infarction patients with or without diabetes mellitus(DM). Methods Two hundred and fifty six patients with cerebral infarction admitted to the first people’s hospital of Foshan from June 2016 to May 2018 were enrolled in the case group, while 208 subjects from medical examination center were enrolled in the control group. Genotyping for the MTHFR C677 T polymorphism was analyzed by PCR-RFLP. Plasma Hey level was mesured by the circulating enzymatic method.Distribution of MTHFR C677 T genotype in two groups and plasma Hey level in two genotype subjects were analyzed. Results Among the 256 patients with cerebral infartion, CC genotype was 136 cases(53.1%), CT genotype was 89 cases( 34.8%), TT genotype was 31 cases( 12.1%), which was significantly different from the control group(χ2=12.821, P < 0.001). The T allele frequencies in case group was higher than that in the control group(29.5% vs. 19.2%,χ2=12.927, P < 0.001). The distributions of genotype between DM group and NDM group was significantly different(χ2 = 16.667,P< 0.001). The T allele frequencies in DM group was significantly higher than that in the NDM group(43.4% vs. 24.5%, χ2 = 17.183,P < 0.001). The Hey level in cases group was higer than that in the control group with different genotypes(P < 0.05). The Hey level of TT genotype patients was higher than that in patients with CC genotype and CT genotype, respectively(F = 26.291, P < 0.001).The level of plasma Hey in DM group was lower than that in NDM group, but with no significant difference(t = 1.578, P =0.116). Hey level in patients with TT genotype in DM group was significantly lower than that in NDM group(t =2.929, P = 0.007). Conclusions MTHFR gene C677 T polymorphism was related to hyperhomocysteine, and may serve as the risk factor of cerebral infarction. The TT type patients with DM may have high risk of cerebral infarction even with low plasma Hcy level, who should be should be paid attention in clinical practice.